TETRASOMY-21-PTER-]Q22.1 AND DOWN-SYNDROME - MOLECULAR DEFINITION OF THE REGION

Down syndrome is usually caused by complete trisomy 21. Rarely, it is due to partial trisomy of the segment 21q22. We report on a 33-month-o ld girl with tetrasomy 21 pter --> q22.1 resulting from an extra chrom osome idic(21)(q22.1). She has craniofacial traits typical of Down syn drome, including brachycephaly, third fontanel, upward slanting palpeb ral fissures, round face, and protruding tongue. Speech development is quite delayed whereas motor development is only mildly retarded. The molecular content of the extra isodicentric chromosome was defined by molecular genetic investigations using 13 single copy probes unique to chromosome 21, and SOD1 expression studies. The child was found to ha ve 4 copies of the region defined by D21S16 (21cen) through D21S93 on 21q22.1 and two copies of the remaining region defined by SOD1 --> D21 S55 -->, D21S123. In view of the recent assignment of Down syndrome fa cial characters to the 21q22 region, defined in part by D21S55, it is significant that this child shows a subset of Down syndrome facial man ifestations, without duplication of this region. These results suggest that genes contributing to the facial and some of the hand manifestat ions of Down syndrome also exist in the chromosomal region proximal to D21S55 in band 21q22.1. (C) 1994 Wiley-Liss, Inc.